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Università della Svizzera italiana

Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells

Ronchi, Francesca ; Basso, Camilla ; Preite, Silvia ; Reboldi, Andrea ; Baumjohann, Dirk ; Perlini, Luana ; Lanzavecchia, Antonio ; Sallusto, Federica

In: Nature communications, 2016, vol. 7, p. 11541

CD4+ Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that experimental priming of encephalitogenic Th cells expressing RORγt and T-bet and producing IL-17A, IFN-γ and GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence of pertussis toxin (PTX) at the...

Università della Svizzera italiana

Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis

De Benedictis, Paola ; Minola, Andrea ; Rota Nodari, Elena ; Aiello, Roberta ; Zecchin, Barbara ; Salomoni, Angela ; Foglierini, Mathilde ; Agatic, Gloria ; Vanzetta, Fabrizia ; Lavenir, Rachel ; Lepelletier, Anthony ; Bentley, Emma ; Weiss, Robin ; Cattoli, Giovanni ; Capua, Ilaria ; Sallusto, Federica ; Wright, Edward ; Lanzavecchia, Antonio ; Bourhy, Hervé ; Corti, Davide

In: EMBO molecular medicine, 2016, vol. 8, no. 4, p. 407-421

Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a...

Università della Svizzera italiana

Serum immunoglobulin a cross-strain blockade of human noroviruses

Lindesmith, Lisa C. ; Beltramello, Martina ; Swanstrom, Jesica ; Jones, Taylor A. ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Open forum infectious diseases, 2015, vol. 2, no. 3, p. ofv084

Background: Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods: Immunoglobulin (Ig)A was purified...

Università della Svizzera italiana

Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

Piccoli, Luca ; Campo, Ilaria ; Fregni, Chiara Silacci ; Fernandez Rodriguez, Blanca Maria ; Minola, Andrea ; Sallusto, Federica ; Luisetti, Maurizio ; Corti, Davide ; Lanzavecchia, Antonio

In: Nature communications, 2015, vol. 6, p. 7375

Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF...

Università della Svizzera italiana

ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells

Mele, Federico ; Basso, Camilla ; Leoni, Cristina ; Aschenbrenner, Dominik ; Becattini, Simone ; Latorre, Daniela ; Lanzavecchia, Antonio ; Sallusto, Federica ; Monticelli, Silvia

In: Nature communications, 2015, vol. 6, p. 6431

T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset. In human memory TH17 cells, miR-181a...

Università della Svizzera italiana

The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells

Gupta, Sandeep ; Gach, Johannes S. ; Becerra, Juan C. ; Phan, Tran B. ; Pudney, Jeffrey ; Moldoveanu, Zina ; Joseph, Sarah B. ; Landucci, Gary ; Supnet, Medalyn Jude ; Ping, Li-Hua ; Corti, Davide ; Moldt, Brian ; Hel, Zdenek ; Lanzavecchia, Antonio ; Ruprecht, Ruth M. ; Burton, Dennis R. ; Mestecky, Jiri ; Anderson, Deborah J. ; Forthal, Donald N.

In: Plos pathogens, 2013, vol. 9, no. 11, p. e1003776

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env- specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis...

Università della Svizzera italiana

Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone

Pickett, Julie E. ; Thompson, John M. ; Sadowska, Agnieszka ; Tkaczyk, Christine ; Sellman, Bret R. ; Minola, Andrea ; Corti, Davide ; Lanzavecchia, Antonio ; Miller, Lloyd S. ; Thorek, Daniel LJ

In: Bone research, 2018, vol. 6, p. 13

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in...

Università della Svizzera italiana

Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection

Lilleri, Daniele ; Kabanova, Anna ; Revello, Maria Grazia ; Percivalle, Elena ; Sarasini, Antonella ; Genini, Emilia ; Sallusto, Federica ; Lanzavecchia, Antonio ; Corti, Davide ; Gerna, Giuseppe

In: Plos one, 2013, vol. 8, no. 3, p. e59863

Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and...

Università della Svizzera italiana

Therapeutic efficacy of antibodies lacking FcγR against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies

Williams, Katherine L. ; Sukupolvi-Petty, Soila ; Beltramello, Martina ; Johnson, Syd ; Sallusto, Federica ; Lanzavecchia, Antonio ; Diamond, Michael S. ; Harris, Eva

In: Plos pathogens, 2013, vol. 9, no. 2, p. e1003157

Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV). At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs) and their modified variants lacking effector...

Università della Svizzera italiana

Rational engineering of a human anti-dengue antibody through experimentally validated computational docking

Simonelli, Luca ; Pedotti, Mattia ; Beltramello, Martina ; Livoti, Elsa ; Calzolai, Luigi ; Sallusto, Federica ; Lanzavecchia, Antonio ; Varani, Luca

In: Plos one, 2013, vol. 8, no. 2, p. e55561

Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and ...